Lycium barbarum glycopeptide protects against inherited retinal degeneration in rd10 mice by regulating phototransduction and neuroinflammatory pathways

Abstract

Inherited retinal degenerative diseases, such as retinitis pigmentosa, cause progressive photoreceptor loss and irreversible vision decline, yet effective treatments remain unavailable. Our previous studies demonstrated that Lycium barbarum glycopeptide delays photoreceptor degeneration in a chemically induced retinitis pigmentosa model, primarily through antiinflammatory mechanisms. In this study, we extended these findings to an inherited retinitis pigmentosa model to further elucidate the neuroprotective actions of Lycium barbarum glycopeptide. Lycium barbarum glycopeptide was orally administered daily to rd10 mice beginning at postnatal day 8, prior to photoreceptor degeneration, and retinal function and morphology were evaluated at postnatal day 25, the peak of rod apoptosis. Behavioral assays, electroretinography, immunofluorescence staining, proteomic profiling, and western blotting were performed to assess the therapeutic effects and molecular mechanisms of Lycium barbarum glycopeptide. Lycium barbarum glycopeptide treatment significantly improved visual performance in rd10 mice, as shown by enhanced optomotor responses and black.white transition behavior. Electroretinography analysis revealed increased scotopic a-wave amplitudes, indicating improved photoreceptor function. Histological evaluation showed preservation of outer nuclear layer thickness and maintenance of rod and cone opsin expression. Lycium barbarum glycopeptide also reduced microglial and Muller glial activation in a region-dependent manner. Proteomic and biochemical analyses revealed that Lycium barbarum glycopeptide upregulated key phototransduction proteins while concurrently downregulating pro-inflammatory mediators such as interleukin-6, nuclear factor kappa B, cyclooxygenase-2, and tumor necrosis factor-α. Collectively, these results demonstrate that Lycium barbarum glycopeptide protects against inherited photoreceptor degeneration by improving retinal function and structure, alleviating neuroinflammation, and supporting phototransduction recovery. This work extends our previous findings and highlights Lycium barbarum glycopeptide as a promising therapeutic candidate for inherited retinal degenerative diseases.